Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer
Background: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396420302358 |
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| author | Kenji Fujiyoshi Juha P. Väyrynen Jennifer Borowsky David J. Papke, Jr. Kota Arima Koichiro Haruki Junko Kishikawa Naohiko Akimoto Tomotaka Ugai Mai Chan Lau Simeng Gu Shanshan Shi Melissa Zhao Annacarolina Fabiana Lucia Da Silva Tyler S. Twombly Hongmei Nan Jeffrey A. Meyerhardt Mingyang Song Xuehong Zhang Kana Wu Andrew T. Chan Charles S. Fuchs Jochen K. Lennerz Marios Giannakis Jonathan A. Nowak Shuji Ogino |
| author_facet | Kenji Fujiyoshi Juha P. Väyrynen Jennifer Borowsky David J. Papke, Jr. Kota Arima Koichiro Haruki Junko Kishikawa Naohiko Akimoto Tomotaka Ugai Mai Chan Lau Simeng Gu Shanshan Shi Melissa Zhao Annacarolina Fabiana Lucia Da Silva Tyler S. Twombly Hongmei Nan Jeffrey A. Meyerhardt Mingyang Song Xuehong Zhang Kana Wu Andrew T. Chan Charles S. Fuchs Jochen K. Lennerz Marios Giannakis Jonathan A. Nowak Shuji Ogino |
| author_sort | Kenji Fujiyoshi |
| collection | DOAJ |
| description | Background: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. Findings: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31–0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57–2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. Interpretation: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion. |
| first_indexed | 2024-12-13T01:04:21Z |
| format | Article |
| id | doaj.art-36f00dc68e4c4aca9c93d5fc3721bf2b |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T01:04:21Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-36f00dc68e4c4aca9c93d5fc3721bf2b2022-12-22T00:04:35ZengElsevierEBioMedicine2352-39642020-07-0157102860Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancerKenji Fujiyoshi0Juha P. Väyrynen1Jennifer Borowsky2David J. Papke, Jr.3Kota Arima4Koichiro Haruki5Junko Kishikawa6Naohiko Akimoto7Tomotaka Ugai8Mai Chan Lau9Simeng Gu10Shanshan Shi11Melissa Zhao12Annacarolina Fabiana Lucia Da Silva13Tyler S. Twombly14Hongmei Nan15Jeffrey A. Meyerhardt16Mingyang Song17Xuehong Zhang18Kana Wu19Andrew T. Chan20Charles S. Fuchs21Jochen K. Lennerz22Marios Giannakis23Jonathan A. Nowak24Shuji Ogino25Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Surgery, Kurume University, Kurume, Fukuoka, JapanProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, FinlandProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADepartment of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USADepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Illinois, USA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Illinois, USADepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USAClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USAClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USAYale Cancer Center, New Haven, Connecticut, USA; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA; Smilow Cancer Hospital, New Haven, Connecticut, USADepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USADepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USAProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, USA; Corresponding author at: Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., EBRC Room 404A, Boston, Massachusetts 02115, USA .Background: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. Findings: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31–0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57–2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. Interpretation: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion.http://www.sciencedirect.com/science/article/pii/S2352396420302358adenocarcinomaartificial intelligence, clinical outcomesepithelial mesenchymal transitionhost-tumour interactionmolecular pathological epidemiology |
| spellingShingle | Kenji Fujiyoshi Juha P. Väyrynen Jennifer Borowsky David J. Papke, Jr. Kota Arima Koichiro Haruki Junko Kishikawa Naohiko Akimoto Tomotaka Ugai Mai Chan Lau Simeng Gu Shanshan Shi Melissa Zhao Annacarolina Fabiana Lucia Da Silva Tyler S. Twombly Hongmei Nan Jeffrey A. Meyerhardt Mingyang Song Xuehong Zhang Kana Wu Andrew T. Chan Charles S. Fuchs Jochen K. Lennerz Marios Giannakis Jonathan A. Nowak Shuji Ogino Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer EBioMedicine adenocarcinoma artificial intelligence, clinical outcomes epithelial mesenchymal transition host-tumour interaction molecular pathological epidemiology |
| title | Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer |
| title_full | Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer |
| title_fullStr | Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer |
| title_full_unstemmed | Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer |
| title_short | Tumour budding, poorly differentiated clusters, and T-cell response in colorectal cancer |
| title_sort | tumour budding poorly differentiated clusters and t cell response in colorectal cancer |
| topic | adenocarcinoma artificial intelligence, clinical outcomes epithelial mesenchymal transition host-tumour interaction molecular pathological epidemiology |
| url | http://www.sciencedirect.com/science/article/pii/S2352396420302358 |
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